Modulation by suramin of NK and monocytic cell-mediated cytotoxicity in human and murine cells

Abstract

The in vitro effects of suramin, a compound recently tested in AIDS treatment, were investigated on human and murine NK and monocyte macrophage cytotoxicity and monocyte migratory ability. In a short-term, TNF-dependent assay, pre-exposure (4–18 h) to 100–400 μg/ml suramin was associated with a markedly increased cytotoxicity by human monocytes and murine-elicited peritoneal macrophages, paralleled by a greater cytotoxic capacity in the supernates of these effectors. Preincubation with the same pharmacological suramin concentration also resulted in enhanced spontaneous and directed migration in monocytic cells. Suramin-preincubated human PBL and murine splenocytes were unchanged in their basal NK cytotoxicity but exhibited a deficient response to IFN. Pre- and post-incubations with suramin resulted in increased macrophagic cytotoxicity for TNF-insensitive targets. Conversely, postincubation of effectors with the drug at 100–400 μg/ml was associated with profound decreases in both NK and TNF-mediated macrophagic cytotoxicities, and prior exposure to suramin of macrophagic supernates resulted in reduced cytotoxic activity. The mechanisms involved in the complex modulatory activity of suramin for monocyte macrophages and NK cells and the possible therapeutic implications of these findings are discussed.